The next wave of cellular immunotherapies in pancreatic cancer

Yeo, Dannel; Giardina, Caroline; Saxena, Payal; Rasko, John E.J.

doi:10.1016/j.omto.2022.01.010

Cited by 40 publications

(30 citation statements)

References 147 publications

(188 reference statements)

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“…Moreover, HER-2 and EGFR-targeted CAR-T cell therapies demonstrated toxicity not only for tumor cells but also for normal cells that shared the antigen (on-Target, off-Tumor Toxicity). Unfortunately, CAR-T cells are currently approved only for hematological malignancies [ 61 ].…”

Section: Immunotherapy In Pancreatic Adenocarcinomamentioning

confidence: 99%

Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer—Current Treatment Options and Future Perspectives

Koustas

Trifylli

Sarantis

et al. 2022

IJMS

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Gastrointestinal (GI) cancer constitutes a highly lethal entity among malignancies in the last decades and is still a major challenge for cancer therapeutic options. Despite the current combinational treatment strategies, including chemotherapy, surgery, radiotherapy, and targeted therapies, the survival rates remain notably low for patients with advanced disease. A better knowledge of the molecular mechanisms that influence tumor progression and the development of optimal therapeutic strategies for GI malignancies are urgently needed. Currently, the development and the assessment of the efficacy of immunotherapeutic agents in GI cancer are in the spotlight of several clinical trials. Thus, several new modalities and combinational treatments with other anti-neoplastic agents have been identified and evaluated for their efficiency in cancer management, including immune checkpoint inhibitors, adoptive cell transfer, chimeric antigen receptor (CAR)-T cell therapy, cancer vaccines, and/or combinations thereof. Understanding the interrelation among the tumor microenvironment, cancer progression, and immune resistance is pivotal for the optimal therapeutic management of all gastrointestinal solid tumors. This review will shed light on the recent advances and future directions of immunotherapy for malignant tumors of the GI system.

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Section: Immunotherapy In Pancreatic Adenocarcinomamentioning

confidence: 99%

Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer—Current Treatment Options and Future Perspectives

Koustas

Trifylli

Sarantis

et al. 2022

IJMS

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“…This has drastically held up the identification of target antigens in PDAC ( 129 ). Despite these limitations, a number of targetable antigens suitable for cellular immunotherapy are currently being tested in both preclinical and clinical studies and include CEA, CD24, HER2, PSCA, MUC1, and MSLN ( 205 , 206 ). Given the complexity of PDAC and its TME, and generally, to expand the use of CAR T cell therapy to solid cancers, cellular immunotherapies are also being explored in combination with other therapeutic approaches ( 207 , 208 ).…”

Section: Therapeutic Strategies: How Can We Harness Our Knowledge Abo...mentioning

confidence: 99%

Understanding Tricky Cellular and Molecular Interactions in Pancreatic Tumor Microenvironment: New Food for Thought

Agostini

Orlacchio²,

Carbone³

et al. 2022

Front. Immunol.

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Pancreatic ductal adenocarcinoma (PDAC) represents 90% of all pancreatic cancer cases and shows a high mortality rate among all solid tumors. PDAC is often associated with poor prognosis, due to the late diagnosis that leads to metastasis development, and limited efficacy of available treatments. The tumor microenvironment (TME) represents a reliable source of novel targets for therapy, and even if many of the biological interactions among stromal, immune, and cancer cells that populate the TME have been studied, much more needs to be clarified. The great limitation in the efficacy of current standard chemoterapy is due to both the dense fibrotic inaccessible TME barrier surrounding cancer cells and the immunological evolution from a tumor-suppressor to an immunosuppressive environment. Nevertheless, combinatorial therapies may prove more effective at overcoming resistance mechanisms and achieving tumor cell killing. To achieve this result, a deeper understanding of the pathological mechanisms driving tumor progression and immune escape is required in order to design rationale-based therapeutic strategies. This review aims to summarize the present knowledge about cellular interactions in the TME, with much attention on immunosuppressive functioning and a specific focus on extracellular matrix (ECM) contribution.

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“…PC is a highly aggressive disease that is expected to be the second leading cancer-related cause of death worldwide by 2030, usually presenting as a locally advanced or metastatic disease with a lack of effective treatments ( 116 ). It was shown that knockdown of METTL3 enhances PC sensitivity to chemotherapeutic drugs but has little effect on cell proliferation.…”

Section: M6a Modification and Solid Tumorsmentioning

confidence: 99%

The Potential Value of m6A RNA Methylation in the Development of Cancers Focus on Malignant Glioma

et al. 2022

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N6-methyladenosine (m6A) RNA methylation is an epigenetic modification that has emerged in the last few years and has received increasing attention as the most abundant internal RNA modification in eukaryotic cells. m6A modifications affect multiple aspects of RNA metabolism, and m6A methylation has been shown to play a critical role in the progression of multiple cancers through a variety of mechanisms. This review summarizes the mechanisms by which m6A RNA methylation induced peripheral cancer cell progression and its potential role in the infiltration of immune cell of the glioblastoma microenvironment and novel immunotherapy. Assessing the pattern of m6A modification in glioblastoma will contribute to improving our understanding of microenvironmental infiltration and novel immunotherapies, and help in developing immunotherapeutic strategies.

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The next wave of cellular immunotherapies in pancreatic cancer

Cited by 40 publications

References 147 publications

Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer—Current Treatment Options and Future Perspectives

Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer—Current Treatment Options and Future Perspectives

Understanding Tricky Cellular and Molecular Interactions in Pancreatic Tumor Microenvironment: New Food for Thought

The Potential Value of m6A RNA Methylation in the Development of Cancers Focus on Malignant Glioma

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